Tourette syndrome (TS) is a neurological disorder characterized by repetitive, stereotyped, involuntary movements and vocalizations called tics. According to the National Institute of Neurological Disorders and Stroke, the first symptoms of TS are almost always noticed in childhood, usually appearing between the ages of 3 and 12. Tics may be classified as either simple or complex. Simple motor tics are sudden, brief, repetitive movements that involve a limited number of muscle groups. Some of the more common simple tics include eye blinking and other eye movements, facial grimacing, shoulder shrugging, and head or shoulder jerking. Simple vocalizations might include repetitive throat-clearing, sniffing, or grunting sounds. Complex tics are distinct, coordinated patterns of movements involving several muscle groups. Complex motor tics might include facial grimacing combined with a head twist and a shoulder shrug. Other complex motor tics may actually appear purposeful, including sniffing or touching objects, hopping, jumping, bending, or twisting. Simple vocal tics may include throat-clearing, sniffing/snorting, grunting, or barking. More complex vocal tics include words or phrases. Perhaps the most dramatic and disabling tics are those that result in self-harm such as punching oneself, or vocal tics including coprolalia (uttering swear words) or echolalia (repeating the words or phrases of others). Medications may be administered to control some symptoms of TS. For example, typical and atypical neuroleptic agents including risperidone, ziprasidone, haloperidol, pimozide and fluphenazine may be utilized but can have long-term and short-term adverse effects. Antihypertensive agents such as clonidine and guanfacine are also used to treat tics.
According to the National Institute on Deafness and Other Communication Disorders (NIDCD) stuttering is a speech disorder characterized by repetition of sounds, syllables, or words; prolongation of sounds; and interruptions in speech known as blocks. An individual who stutters exactly knows what he or she would like to say but has trouble producing a normal flow of speech. These speech disruptions may be accompanied by struggle behaviors, such as rapid eye blinks or tremors of the lips. Stuttering can make it difficult to communicate with other people, which often affects a person's quality of life and interpersonal relationships. Stuttering can also negatively influence job performance and opportunities, and treatment can come at a high financial cost. Symptoms of stuttering can vary significantly throughout a person's day.
Stuttering affects people of all ages. It occurs most often in children between the ages of 2 and 6 as they are developing their language skills. Approximately 5 to 10 percent of all children will stutter for some period in their life, lasting from a few weeks to several years. Approximately 75 percent of children recover from stuttering. For the remaining 25 percent who continue to stutter, stuttering can persist as a lifelong communication disorder.
Stuttering is commonly grouped into two types termed developmental and neurogenic. Developmental stuttering occurs in young children while they are still learning speech and language skills. It is the most common form of stuttering. Most scientists and clinicians believe that developmental stuttering stems from complex interactions of multiple factors. Recent brain imaging studies have shown consistent differences in those who stutter compared to nonstuttering peers. Developmental stuttering may also run in families and research has shown that genetic factors contribute to this type of stuttering. Neurogenic stuttering may occur after a stroke, head trauma, or other type of brain injury. With neurogenic stuttering, the brain has difficulty coordinating the different brain regions involved in speaking, resulting in problems in production of clear, fluent speech.
The U.S. Food and Drug Administration has not approved any drug for the treatment of stuttering. However, some drugs that are approved to treat other health problems—such as epilepsy, anxiety, or depression—have been used to treat stuttering. These drugs often have side effects that make them difficult to use over a long period of time.
Gaboxadol (4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol) (THIP)) is described in EP Patent No. 0000338 and in EP Patent No. 0840601, U.S. Pat. Nos. 4,278,676, 4,362,731, 4,353,910, and WO 2005/094820. Gaboxadol is a selective GABAA receptor agonist with a preference for δ-subunit containing GABAA receptors. In the early 1980s gaboxadol was the subject of a series of pilot studies that tested its efficacy as an analgesic and anxiolytic, as well as a treatment for tardive dyskinesia, Huntington's disease, Alzheimer's disease, and spasticity. In the 1990s gaboxadol moved into late stage development for the treatment of insomnia. The development was discontinued after the compound failed to show significant effects in sleep onset and sleep maintenance in a three-month efficacy study. Additionally, patients with a history of drug abuse who received gaboxadol experienced a steep increase in psychiatric adverse events.